Papers - NAKASE Hiroshi

Single Nucleotide Polymorphisms of the MEFV Gene E148Q Are Highly Associated With Disease Phenotype in Crohn's Disease.

Satoshi Yamada, Yusuke Honzawa, Shuji Yamamoto, Minoru Matsuura, Hiroki Kitamoto, Makoto Okabe, Nobuyuki Kakiuchi, Takahiko Toyonaga, Taku Kobayashi, Toshifumi Hibi, Hiroshi Seno, Hiroshi Nakase

Inflammatory bowel diseases    2023.11  [International journal]

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BACKGROUND: Single nucleotide polymorphisms (SNPs) of the MEFV gene may modify inflammatory bowel disease (IBD) activity. The prevalence of MEFV gene SNPs in IBD patients and their involvement in IBD pathophysiology remains unclear. METHODS: We analyzed 12 MEFV gene SNPs in peripheral leukocytes of Japanese IBD patients (Crohn's disease [CD]: 69 patients, ulcerative colitis: 32 patients) by polymerase chain reaction using next-generation DNA sequencing and evaluated their prevalence and association with the disease characteristics. Inflammasome activity and mature interleukin (IL)-1β and IL-18 production were evaluated in peripheral blood mononuclear cells obtained from CD patients stimulated with lipopolysaccharides and adenosine triphosphate, and compared between those with and without the E148Q SNP. COL1A1 and HSP47 gene expression was analyzed in CCD-18Co cells costimulated with IL-1β and other inflammatory cytokines. RESULTS: The prevalence of MEFV gene SNPs in IBD patients was similar to that in the human gene database. E148Q was the most common SNP. Compared with CD patients without E148Q, those with E148Q had a significantly greater frequency of the stricture phenotype, and their peripheral blood mononuclear cells exhibited significantly higher IL-1β and IL-18 levels and higher caspase-1 activity. IL-1β and IL-17A synergistically increased COL1A1 and HSP47 gene expression. CONCLUSIONS: MEFV gene SNPs, including E148Q, modify the behavior of CD. IL-1β and IL-18 are produced through enhanced caspase-1 activity in monocytes of CD patients with E148Q. IL-1β promotes gene expression of fibrosis-related genes by cooperating with IL-17A in myofibroblasts. Therefore, E148Q might be a disease-modifying gene associated with the fibrostenosis phenotype in CD patients.

DOI PubMed

A case of IgG4-related cholecystitis diagnosed by transpapillary gallbladder biopsy using a novel device delivery system

Yujiro Kawakami, Naohiro Kameyama, Yosuke Hirobe, Yoshiharu Masaki, Ayako Murota, Shintaro Sugita, Hiroshi Nakase

Endoscopy ( Georg Thieme Verlag KG )  55 ( S 01 ) E1108 - E1110  2023.10

DOI

高齢者切除可能膵癌に対する術前化学療法の有用性の検証

柾木 喜晴, 川上 裕次郎, 我妻 康平, 石上 敬介, 室田 文子, 吉田 真誠, 木村 康利, 仲瀬 裕志

日本消化器病学会雑誌 ( (一財)日本消化器病学会 )  120 ( 臨増大会 ) A849 - A849  2023.10

切除不能肝細胞癌に対する分子標的治療症例の複数レジメン治療の有用性

阿久津 典之, 沼田 泰尚, 平野 雄大, 我妻 康平, 川上 裕次郎, 柾木 喜晴, 石上 敬介, 室田 文子, 佐々木 茂, 仲瀬 裕志

日本消化器病学会雑誌 ( (一財)日本消化器病学会 )  120 ( 臨増大会 ) A814 - A814  2023.10

後腹膜線維症・動脈周囲炎に対するEUS-FNA

川上 裕次郎, 柾木 喜晴, 室田 文子, 阿久津 典之, 仲瀬 裕志

Gastroenterological Endoscopy ( (一社)日本消化器内視鏡学会 )  65 ( Suppl.2 ) 2042 - 2042  2023.10

難治性消化器免疫疾患 IgG4関連疾患における消化管生検の検討

平野 雄大, 川上 裕次郎, 石上 敬介, 柾木 喜晴, 室田 文子, 阿久津 典之, 佐々木 茂, 仲瀬 裕志

日本臨床免疫学会総会プログラム・抄録集 ( (一社)日本臨床免疫学会 )  51回   69 - 69  2023.10

Systemic mastocytosis observed by image-enhanced endoscopy

Ryota Seto, Shinji Yoshii, Tomoe Kazama, Tsukasa Yamakawa, Shintaro Sugita, Hiro-o Yamano, Hiroshi Nakase

American Journal of Gastroenterology ( Ovid Technologies (Wolters Kluwer Health) )   2023.09

DOI

血清可溶性Fas値と肝臓癌罹患リスク(Serum soluble Fas levels and incidence of liver cancer)

足立 靖, 野島 正寛, 森 満, 久保 俊之, 阿久津 典之, 佐々木 泰史, 仲瀬 裕志, 遠藤 高夫, 林 櫻松, 若井 建志, 玉腰 暁子

日本癌学会総会記事 ( (一社)日本癌学会 )  82回   125 - 125  2023.09

特発性血小板減少性紫斑病(ITP)を合併しTPO受容体作動薬(TPO-RA)を使用することでGnP療法が施行可能となった膵癌の1例

常盤 孝介, 室田 文子, 平野 雄大, 我妻 康平, 川上 裕次郎, 沼田 泰尚, 石上 敬介, 柾木 喜晴, 阿久津 典之, 村瀬 和幸, 佐々木 茂, 仲瀬 裕志

日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集 ( 日本消化器病学会-北海道支部 )  133回・127回   56 - 56  2023.09

Trajectory analyses to identify persistently low responders to COVID-19 vaccination in patients with inflammatory bowel disease: a prospective multicentre controlled study, J-COMBAT.

Kenji Watanabe, Masanori Nojima, Hiroshi Nakase, Toshiyuki Sato, Minoru Matsuura, Nobuo Aoyama, Taku Kobayashi, Hirotake Sakuraba, Masakazu Nishishita, Kaoru Yokoyama, Motohiro Esaki, Fumihito Hirai, Masakazu Nagahori, Sohachi Nanjo, Teppei Omori, Satoshi Tanida, Yoshihiro Yokoyama, Kei Moriya, Atsuo Maemoto, Osamu Handa, Naoki Ohmiya, Kiichiro Tsuchiya, Shinichiro Shinzaki, Shingo Kato, Toshio Uraoka, Hiroki Tanaka, Noritaka Takatsu, Atsushi Nishida, Junji Umeno, Masanao Nakamura, Yoshiyuki Mishima, Mikihiro Fujiya, Kenji Tsuchida, Sakiko Hiraoka, Makoto Okabe, Takahiko Toyonaga, Katsuyoshi Matsuoka, Akira Andoh, Yoshio Hirota, Tadakazu Hisamatsu

Journal of gastroenterology    2023.08  [Domestic journal]

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BACKGROUND: The degree of immune response to COVID-19 vaccination in inflammatory bowel disease (IBD) patients based on actual changes in anti-SARS-CoV-2 antibody titres over time is unknown. METHODS: Data were prospectively acquired at four predetermined time points before and after two vaccine doses in a multicentre observational controlled study. The primary outcome was humoral immune response and vaccination safety in IBD patients. We performed trajectory analysis to identify the degree of immune response and associated factors in IBD patients compared with controls. RESULTS: Overall, 645 IBD patients and 199 control participants were analysed. At 3 months after the second vaccination, the seronegative proportions were 20.3% (combination of anti-tumour necrosis factor [TNF]α and thiopurine) and 70.0% (triple combination including steroids), despite that 80.0% receiving the triple combination therapy were seropositive at 4 weeks after the second vaccination. Trajectory analyses indicated three degrees of change in immune response over time in IBD patients: high (57.7%), medium (35.6%), and persistently low (6.7%). In the control group, there was only one degree, which corresponded with IBD high responders. Older age, combined anti-TNFα and thiopurine (odds ratio [OR], 37.68; 95% confidence interval [CI], 5.64-251.54), steroids (OR, 21.47; 95%CI, 5.47-84.26), and tofacitinib (OR, 10.66; 95%CI, 1.49-76.31) were factors associated with persistently low response. Allergy history (OR, 0.17; 95%CI, 0.04-0.68) was a negatively associated factor. Adverse reactions after the second vaccination were significantly fewer in IBD than controls (31.0% vs 59.8%; p < 0.001). CONCLUSIONS: Most IBD patients showed a sufficient immune response to COVID-19 vaccination regardless of clinical factors. Assessment of changes over time is essential to optimize COVID-19 vaccination, especially in persistently low responders.

DOI PubMed

新規ナトリウム利尿ペプチド薬の開発と臨床応用

市来 智子, 沼田 泰尚, 佐々木 茂, 辻 喜久, 仲瀬 裕志

細胞 ( (株)ニュー・サイエンス社 )  55 ( 9 ) 714 - 717  2023.08

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ナトリウム利尿ペプチド(Natriuretic Peptide,NP)は心臓・血管内皮など体内で生成される内分泌ホルモンである。ヒトにはANP,BNP,CNPの3種類のNPが存在し,ナトリウム利尿,血管拡張,レニン・アンジオテンシン・アルドステロン系の抑制,心筋肥大や線維化抑制など多彩な生理作用を有し,治療薬としての臨床応用を目指した創薬ターゲットとなっている。NPの創薬では,元来の構造を変化させることで分解を抑制し長期投与に耐えられるペプチドや,複数のレセプターを刺激し多彩な薬理作用を期待できるようなペプチドが合成されている。内因性NPの半減期を延長する経口薬も開発されており,既に心不全や小人症を対象とする薬剤が薬事承認された。NPを用いた新しい治療ターゲットとしてメタボリックシンドロームの関連疾患群も注目されている。本稿ではNPの生理作用,創薬開発及び今後の展望に関して論じる。(著者抄録)

TM4SF1-AS1 inhibits apoptosis by promoting stress granule formation in cancer cells

Hiroshi Kitajima, Reo Maruyama, Takeshi Niinuma, Eiichiro Yamamoto, Akira Takasawa, Kumi Takasawa, Kazuya Ishiguro, Akihiro Tsuyada, Ryo Suzuki, Gota Sudo, Toshiyuki Kubo, Kei Mitsuhashi, Masashi Idogawa, Shoichiro Tange, Mutsumi Toyota, Ayano Yoshido, Kohei Kumegawa, Masahiro Kai, Kazuyoshi Yanagihara, Takashi Tokino, Makoto Osanai, Hiroshi Nakase, Hiromu Suzuki

Cell Death &amp; Disease ( Springer Science and Business Media LLC )  14 ( 7 )  2023.07

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Abstract Long noncoding RNAs (lncRNAs) play pivotal roles in tumor development. To identify dysregulated lncRNAs in gastric cancer (GC), we analyzed genome-wide trimethylation of histone H3 lysine 4 (H3K4me3) to screen for transcriptionally active lncRNA genes in the non-tumorous gastric mucosa of patients with GC and healthy individuals. We found that H3K4me3 at TM4SF1-AS1 was specifically upregulated in GC patients and that the expression of TM4SF1-AS1 was significantly elevated in primary and cultured GC cells. TM4SF1-AS1 contributes to GC cell growth in vitro and in vivo, and its oncogenic function is mediated, at least in part, through interactions with purine-rich element-binding protein α (Pur-α) and Y-box binding protein 1 (YB-1). TM4SF1-AS1 also activates interferon signaling in GC cells, which is dependent on Pur-α and RIG-I. Chromatin isolation by RNA purification (ChIRP)-mass spectrometry demonstrated that TM4SF1-AS1 was associated with several stress granule (SG)-related proteins, including G3BP2, RACK1, and DDX3. Notably, TM4SF1-AS1 promoted SG formation and inhibited apoptosis in GC cells by sequestering RACK1, an activator of the stress-responsive MAPK pathway, within SGs. TM4SF1-AS1-induced SG formation and apoptosis inhibition are dependent on Pur-α and YB-1. These findings suggested that TM4SF1-AS1 contributes to tumorigenesis by enhancing SG-mediated stress adaptation.

DOI

A novel approach to diagnosing crystal-storing histiocytosis: utility of scanning electron microscopy for formalin-fixed paraffin-embedded tissue specimens.

Kazufumi Magara, Akira Takasawa, Keisuke Kikuchi, Taro Sugawara, Taro Murakami, Daisuke Kyuno, Yusuke Ono, Kumi Takasawa, Yasunao Numata, Shigeru Sasaki, Hiroshi Nakase, Tadashi Hasegawa, Makoto Osanai

Medical molecular morphology    2023.07  [Domestic journal]

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Crystal-storing histiocytosis (CSH) is a rare disorder that shows infiltration of histiocytes with an aberrant cytoplasmic accumulation of crystalline structures and is often accompanied by lymphoproliferative-plasma cell disorders (LP-PCD) as background diseases. The diagnosis of CSH requires identification of crystalline structures that accumulate in the infiltrating histiocytes, which may be challenging by optical microscopy alone. In this case report, we describe an atypical course of systemic CSH with multifocal fibrosclerosis of an unknown background disease that was diagnosed by ultrastructural observation, including transmission electron microscopy (TEM) and scanning electron microscopy (SEM), in pathological autopsy. In addition, crystalline structures were successfully identified by scanning electron microscopic observations using formalin-fixed and paraffin-embedded (FFPE) tissue from biopsy specimens taken before death. Since CSH was identified by SEM in a tiny biopsy specimen, observation of histiocytic infiltrative lesions by SEM using FFPE tissue may lead to early detection of and initiation of treatment for CSH.

DOI PubMed

Immunoglobulin G4-related periarteritis successfully diagnosed by endoscopic ultrasonography-guided fine-needle biopsy.

Yujiro Kawakami, Yosuke Hirobe, Hiroshi Nakase

Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society   35 ( 5 ) e87-e89  2023.07  [International journal]

DOI PubMed

高齢者肝細胞癌に対する経皮的ラジオ波焼灼療法の検討

沼田 泰尚, 阿久津 典之, 我妻 康平, 平野 雄大, 川上 裕次郎, 石上 敬介, 柾木 喜晴, 室田 文子, 佐々木 茂, 仲瀬 裕志

日本高齢消化器病学会誌 ( (NPO)日本高齢消化器病学会 )  26 ( 1 ) 134 - 134  2023.07

Generalized crystal-storing histiocytosis with noncirrhotic portal hypertension: an autopsy case report.

Yasunao Numata, Shigeru Sasaki, Kazufumi Magara, Akira Takasawa, Taro Sugawara, Naruki Ohara, Noriyuki Akutsu, Tadashi Hasegawa, Makoto Osanai, Hiroshi Nakase

Clinical journal of gastroenterology   16 ( 3 ) 450 - 456  2023.04  [Domestic journal]

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Crystal-storing histiocytosis (CSH) is a rare disease associated with the accumulation of histiocytes containing crystalline matter within their cytoplasm. Herein, we present the case of a female patient who was diagnosed with Tolosa-Hunt syndrome at 45 years of age and idiopathic retroperitoneal fibrosis when she was 48 years. She developed portal hypertension (PH), but did not present with cirrhosis; as such, the cause of PH was not identified. Her PH gradually worsened when she was 54 years, and at the age of 60 years, she died from an acute subdural hematoma. Autopsy revealed retroperitoneal fibrosis with severe fibrosis extending around the hepatic veins and into the porta hepatis. Histologically, the retroperitoneal tissue showed a dense infiltrate of eosinophilic histiocytes with crystal structures in the cytoplasm, which was pathologically diagnosed as CSH. Nodular regenerative hyperplasia was observed in the liver parenchyma, whereas cirrhosis was not. In the present case, CSH caused fibrosis, which was believed to be the cause of PH. In addition, we considered that nodular regenerative hyperplasia caused by the altered hepatic blood flow due to treatment of gastric varices contributed to worsening PH. Hence, CSH should be considered as an underlying disease in noncirrhotic portal hypertension.

DOI PubMed

Ischemia-induced intestinal de-epithelization and consequent cholangitis lenta after usage of extracorporeal membrane oxygenation in COVID-19 patients: an autopsy series

Sae Hatanaka, Yuki Yamada, Terufumi Kubo, Kazufumi Magara, Yusuke Ono, Shintaro Sugita, Tomohide Tsukahara, Daisuke Kyuno, Michiko Hosaka, Kenta Sasaki, Yoshihiko Hirohashi, Tsukasa Yamakawa, Keisuke Harada, Naofumi Bunya, Eichi Narimatsu, Hiroshi Nakase, Tadashi Hasegawa, Makoto Osanai, Toshihiko Torigoe

Oxford Medical Case Reports ( Oxford University Press (OUP) )  2023 ( 4 )  2023.04

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Abstract Since its discovery in late 2019, severe acute respiratory syndrome coronavirus 2 has spread around the world, causing millions of deaths due to coronavirus disease 2019 (COVID-19). Numerous clinical and post-mortem investigations of COVID-19 cases have found myriad clinical and pathological manifestations of the disease. In this report, we present three autopsy cases in which, despite weaning from extracorporeal membrane oxygenation (ECMO), extensive intestinal epithelial shedding, probably due to ischemia, was followed by massive watery diarrhea and the spread of infection via the portal vein due to bacterial translocation, which resulted in cholangitis lenta. Thrombophilia was attributed to ECMO usage and COVID-19-related vascular endothelial damage. These cases provide instructive findings showing that the loss of the intestinal barrier may be the underlying cause of severe watery diarrhea and liver failure in COVID-19 patients, especially with ECMO usage.

DOI

胆膵内視鏡診療におけるトラブルシューティング 膵管空腸吻合部ロストステントの迷入に対する内視鏡的トラブルシューティング

川上 裕次郎, 柾木 喜晴, 仲瀬 裕志

Gastroenterological Endoscopy ( (一社)日本消化器内視鏡学会 )  65 ( Suppl.1 ) 846 - 846  2023.04

Red blood cell distribution width as a novel marker for predicting bleeding after endoscopic resection for early gastric cancer.

Takada Yumemi, Shinji Yoshii, Tsukasa Yamakawa, Yuki Hayashi, Takakazu Miyake, Yoshihiro Yokoyama, Gota Sudo, Kei Mitsuhashi, Masanori Nojima, Hiro-O Yamano, Hiroshi Nakase

DEN open   3 ( 1 ) e123  2023.04  [International journal]

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OBJECTIVES: Endoscopic resection (ER) is a minimally invasive treatment for early gastric cancer (EGC); however, there is a high occurrence of bleeding. This study aimed to clarify the significance of red blood cell distribution width (RDW) as a predictive risk factor for bleeding after ER for EGC. METHODS: We conducted a retrospective study based on data for patients who underwent ER for EGC from 2019 to 2021. This study included 79 lesions in 54 patients who underwent ER for EGC. The primary outcome was the association between RDW before ER and bleeding within 28 days of treatment. Receiver operating characteristic (ROC) curves were constructed, wherein areas under the curve (AUCs) and 95% confidence intervals were calculated to compare the discriminatory power of RDW for predicting bleeding. RESULTS: Endoscopic submucosal dissection was used as the resection method for 73 lesions, whereas endoscopic mucosal resection was used for six lesions. En bloc resection was performed in all cases. There were no cases of perforation; however, bleeding after ER occurred in five cases (9.3%). ROC curve analysis of bleeding after ER showed that the AUC was 0.843 with a good diagnostic performance. When the cut-off value of RDW was set at 14.4%, sensitivity and specificity were 80% and 85.7%, respectively. There was a bleeding rate of 36.4% (4/11) at an RDW of ≥14.4%, which was significantly higher than that of 2.3% (1/43) at an RDW of <14.4%. CONCLUSION: RDW can be a predictor of bleeding risk after ER for EGC.

DOI PubMed

EUS-FNAが診断に有用であったIgG4関連動脈周囲炎の1例

川上 裕次郎, 我妻 康平, 沼田 泰尚, 石上 敬介, 柾木 喜晴, 室田 文子, 阿久津 典之, 仲瀬 裕志

超音波医学 ( (公社)日本超音波医学会 )  50 ( Suppl. ) S590 - S590  2023.04